The RNA Chaperone Hfq is Essential for the Virulence of Salmonella Typhimurium

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2006 Dec 14

PMID 17163975

Citations 221

Authors

Alexandra Sittka

Verena Pfeiffer

Karsten Tedin

Jorg Vogel

Affiliations

Soon will be listed here.

Abstract

The RNA chaperone, Hfq, plays a diverse role in bacterial physiology beyond its original role as a host factor required for replication of Qbeta RNA bacteriophage. In this study, we show that Hfq is involved in the expression and secretion of virulence factors in the facultative intracellular pathogen, Salmonella typhimurium. A Salmonella hfq deletion strain is highly attenuated in mice after both oral and intraperitoneal infection, and shows a severe defect in invasion of epithelial cells and a growth defect in both epithelial cells and macrophages in vitro. Surprisingly, we find that these phenotypes are largely independent of the previously reported requirement of Hfq for expression of the stationary phase sigma factor, RpoS. Our results implicate Hfq as a key regulator of multiple aspects of virulence including regulation of motility and outer membrane protein (OmpD) expression in addition to invasion and intracellular growth. These pleiotropic effects are suggested to involve a network of regulatory small non-coding RNAs, placing Hfq at the centre of post-transcriptional regulation of virulence gene expression in Salmonella. In addition, the hfq mutation appears to cause a chronic activation of the RpoE-mediated envelope stress response which is likely due to a misregulation of membrane protein expression.

Citing Articles

NlpD as a crucial factor in desiccation resistance and biofilm formation in Cronobacter sakazakii.

Xue J, Meng K, Lv J, Liu L, Duan F, Ji X Sci Rep. 2025; 15(1):6289.

PMID: 39984582 PMC: 11845588. DOI: 10.1038/s41598-025-90905-4.

Metabolic Proteins Expression Up-Regulated in Blood-Borne Extensively Drug-Resistant Typhi Isolates from Pakistan.

Yasin N, Rahman H, Qasim M, Nisa I, Sarwar Y, Khan N Medicina (Kaunas). 2024; 60(9).

PMID: 39336445 PMC: 11433874. DOI: 10.3390/medicina60091404.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

Nickerson C, McLean R, Barrila J, Yang J, Thornhill S, Banken L Microbiol Mol Biol Rev. 2024; 88(3):e0014423.

PMID: 39158275 PMC: 11426028. DOI: 10.1128/mmbr.00144-23.

RNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence.

Wu K, Lin X, Lu Y, Dong R, Jiang H, Svensson S Nat Commun. 2024; 15(1):6946.

PMID: 39138169 PMC: 11322559. DOI: 10.1038/s41467-024-51213-z.

Distinct cell death pathways induced by granzymes collectively protect against intestinal Salmonella infection.

Chawla A, Vandereyken M, Arias M, Santiago L, Dikovskaya D, Nguyen C Mucosal Immunol. 2024; 17(6):1242-1255.

PMID: 39137883 PMC: 11631773. DOI: 10.1016/j.mucimm.2024.08.006.

References

van Asten F, Hendriks H, Koninkx J, van Dijk J . Flagella-mediated bacterial motility accelerates but is not required for Salmonella serotype Enteritidis invasion of differentiated Caco-2 cells. Int J Med Microbiol. 2004; 294(6):395-9. DOI: 10.1016/j.ijmm.2004.07.012. View

Vogel J, Argaman L, Wagner E, Altuvia S . The small RNA IstR inhibits synthesis of an SOS-induced toxic peptide. Curr Biol. 2004; 14(24):2271-6. DOI: 10.1016/j.cub.2004.12.003. View

Hara-Kaonga B, Pistole T . OmpD but not OmpC is involved in adherence of Salmonella enterica serovar typhimurium to human cells. Can J Microbiol. 2005; 50(9):719-27. DOI: 10.1139/w04-056. View

McNealy T, Forsbach-Birk V, Shi C, Marre R . The Hfq homolog in Legionella pneumophila demonstrates regulation by LetA and RpoS and interacts with the global regulator CsrA. J Bacteriol. 2005; 187(4):1527-32. PMC: 545622. DOI: 10.1128/JB.187.4.1527-1532.2005. View

Majdalani N, Vanderpool C, Gottesman S . Bacterial small RNA regulators. Crit Rev Biochem Mol Biol. 2005; 40(2):93-113. DOI: 10.1080/10409230590918702. View

Bang I, Frye J, McClelland M, Velayudhan J, Fang F . Alternative sigma factor interactions in Salmonella: sigma and sigma promote antioxidant defences by enhancing sigma levels. Mol Microbiol. 2005; 56(3):811-23. DOI: 10.1111/j.1365-2958.2005.04580.x. View

Ellermeier C, Ellermeier J, Slauch J . HilD, HilC and RtsA constitute a feed forward loop that controls expression of the SPI1 type three secretion system regulator hilA in Salmonella enterica serovar Typhimurium. Mol Microbiol. 2005; 57(3):691-705. DOI: 10.1111/j.1365-2958.2005.04737.x. View

Udekwu K, Darfeuille F, Vogel J, Reimegard J, Holmqvist E, Wagner E . Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. Genes Dev. 2005; 19(19):2355-66. PMC: 1240044. DOI: 10.1101/gad.354405. View

Rasmussen A, Eriksen M, Gilany K, Udesen C, Franch T, Petersen C . Regulation of ompA mRNA stability: the role of a small regulatory RNA in growth phase-dependent control. Mol Microbiol. 2005; 58(5):1421-9. DOI: 10.1111/j.1365-2958.2005.04911.x. View

10.

Ziolkowska K, Derreumaux P, Folichon M, Pellegrini O, Regnier P, Boni I . Hfq variant with altered RNA binding functions. Nucleic Acids Res. 2006; 34(2):709-20. PMC: 1356530. DOI: 10.1093/nar/gkj464. View

11.

Rhodius V, Suh W, Nonaka G, West J, Gross C . Conserved and variable functions of the sigmaE stress response in related genomes. PLoS Biol. 2005; 4(1):e2. PMC: 1312014. DOI: 10.1371/journal.pbio.0040002. View

12.

Mangan M, Lucchini S, Danino V, Croinin T, Hinton J, Dorman C . The integration host factor (IHF) integrates stationary-phase and virulence gene expression in Salmonella enterica serovar Typhimurium. Mol Microbiol. 2006; 59(6):1831-47. DOI: 10.1111/j.1365-2958.2006.05062.x. View

13.

Romby P, Vandenesch F, Wagner E . The role of RNAs in the regulation of virulence-gene expression. Curr Opin Microbiol. 2006; 9(2):229-36. DOI: 10.1016/j.mib.2006.02.005. View

14.

Skovierova H, Rowley G, Rezuchova B, Homerova D, Lewis C, Roberts M . Identification of the sigmaE regulon of Salmonella enterica serovar Typhimurium. Microbiology (Reading). 2006; 152(Pt 5):1347-1359. DOI: 10.1099/mic.0.28744-0. View

15.

Jones A, Goodwill A, Elliott T . Limited role for the DsrA and RprA regulatory RNAs in rpoS regulation in Salmonella enterica. J Bacteriol. 2006; 188(14):5077-88. PMC: 1539969. DOI: 10.1128/JB.00206-06. View

16.

Navarre W, Porwollik S, Wang Y, McClelland M, Rosen H, Libby S . Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella. Science. 2006; 313(5784):236-8. DOI: 10.1126/science.1128794. View

17.

Hensel M, Shea J, Waterman S, MUNDY R, Nikolaus T, Banks G . Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages. Mol Microbiol. 1998; 30(1):163-74. DOI: 10.1046/j.1365-2958.1998.01047.x. View

18.

Cirillo D, Valdivia R, Monack D, Falkow S . Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Mol Microbiol. 1998; 30(1):175-88. DOI: 10.1046/j.1365-2958.1998.01048.x. View

19.

Vytvytska O, Jakobsen J, Balcunaite G, Andersen J, Baccarini M, von Gabain A . Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability. Proc Natl Acad Sci U S A. 1998; 95(24):14118-23. PMC: 24336. DOI: 10.1073/pnas.95.24.14118. View

20.

Shea J, Beuzon C, Gleeson C, MUNDY R, Holden D . Influence of the Salmonella typhimurium pathogenicity island 2 type III secretion system on bacterial growth in the mouse. Infect Immun. 1998; 67(1):213-9. PMC: 96299. DOI: 10.1128/IAI.67.1.213-219.1999. View